title: Identification of KD5170: a novel mercaptoketone-based histone deacetylase inhibitor.
abstract: We report the identification of KD5170, a potent mercaptoketone-based Class I and II-histone deacetylase inhibitor that demonstrates broad spectrum cytotoxic activity against a range of human tumor-derived cell lines. KD5170 exhibits robust and sustained histone H3 hyperacetylation in HCT-116 xenograft tumors following single oral or i.v. dose and inhibition of tumor growth following chronic dosing.
authors.affiliation: Department of Chemistry, Kalypsys, Inc., 10420 Wateridge Circle, San Diego, CA 92121, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Payne
authors.forename: Céline
authors.initials: C
authors.lastname: Bonnefous
authors.forename: Christian A
authors.initials: CA
authors.lastname: Hassig
authors.forename: Kent T
authors.initials: KT
authors.lastname: Symons
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Phan-Manh
authors.initials: PM
authors.lastname: Nguyen
authors.forename: Tami
authors.initials: T
authors.lastname: Annable
authors.forename: Paul L
authors.initials: PL
authors.lastname: Wash
authors.forename: Timothy Z
authors.initials: TZ
authors.lastname: Hoffman
authors.forename: Tadimeti S
authors.initials: TS
authors.lastname: Rao
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Shiau
authors.forename: James W
authors.initials: JW
authors.lastname: Malecha
authors.forename: Stewart A
authors.initials: SA
authors.lastname: Noble
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Hager
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Smith
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; C530801:KD 5170; D011355:Prodrugs; D011725:Pyridines; D013449:Sulfonamides